Abstract: Objective To study the effects of Ulinastatin on the incidence of pancreatic fistula, levels of inflammatory mediators, immune function and prognosis in patients with pancreatic cancer during perioperative period. Methods A total of 90 patients with pancreatic cancer admitted to our hospital from March 2015 to December 2017 were enrolled and divided into Ulinastatin group A, Ulinastatin group B and control group according to the perioperative management plan, with 30 cases in each group. Ulinastatin was given to Ulinastatin group A for 5 days before and after the surgery. Group B was treated with Ulinastatin for 3 days before and after the surgery, while the control group was given for 3 days before and after the surgery. The peritoneal fluid drainage, amylase content of the drainage fluid, inflammatory mediators, immune index and prognosis of patients were compared among the three groups. Results The intraperitoneal drainage and amylase content of Ulinastatin group A and group B were lower than those of the control group, the difference was statistically significant (all P<0.05), but there was no significant difference between group A and group B. The levels of inflammatory mediators in group A and group B were lower than those in the control group (all P<0.05), but there was no significant difference between group A and group B. The ratio of CD4⁺ lymphocytes to all lymphocytes and the ratio of CD4⁺/CD8⁺ lymphocytes in Ulinastatin group A and group B were significantly higher than those in the control group (all P<0.05). There was no significant difference in CD3⁺ and CD8⁺ among the three groups. The survival rate of Ulinastatin group A and group B was higher than that of the control group. The survival rate of group A was slightly higher than that of group B, which was not statistically significant. Conclusion Ulinastatin can reduce the exudation of pancreatic juice and the incidence of pancreatic fistula in perioperative pancreatic cancer patients, and improve the survival rate and prognosis of patients.